Advertisement

Topics

Molecular Mechanisms of Volume Overload-Aim 1(SCCOR in Cardiac Dysfunction and Disease)

2014-07-23 21:11:03 | BioPortfolio

Summary

The investigators hypothesize that ß1-RB attenuates ECM degradation and progressive adverse LV remodeling and failure in the volume overload of MR. Patients without coronary artery disease and moderate MR, as assessed by color/flow Doppler echocardiography, will be randomized to ß1-RB vs. placebo to address the following aims:

*Aim 1: Establish whether Beta1-RB attenuates adverse LV remodeling compared to placebo in patients with non-surgical, chronic MR. Using 3-dimensional magnetic resonance imaging (MRI) and tissue tagging, LV function and geometry will be assessed at baseline and every 6 months for up to 2 years.

Aim 2: Determine whether indices of inflammation correlate with degree of LV remodeling and whether ß1-RB decrease indices of inflammation and collagen turnover. At the time of MRI, blood samples for collagen breakdown products, MMP activity, and markers of excess production of RIS will be obtained and related to changes in LV remodeling defined by serial 3-dimensional MRI and tissue tagging.

Description

In Western society, the most common causes of chronic mitral regurgitation (MR) are ischemic heart disease and myxomatous degeneration of the valve, resulting in prolapse, ruptured chordae or partial flail leaflet. Current indications for surgery are only for patients with severe MR and either notable symptoms or overt LV dysfunction (ejection fraction < 60%, end-systolic diameter > 40 mm). Therefore, despite the availability of surgery, most patients with MR of moderate severity are not immediate candidates for surgery, warranting analysis of potential beneficial effects of medical treatment. Chronic therapy with vasodilators reduces LV wall stress and thereby delays the need for valve replacement in aortic regurgitation; however, no such data are currently available in patients with chronic MR using standard vasodilators or agents that block the renin angiotensin system (RAS).

In a clinically-relevant dog model of MR, the investigators have shown increased LV ACE and chymase expression, increased LV angiotensin II but, as opposed to pressure overload, there was an absence of fibrosis with net extracellular matrix (ECM) degradation and activation of matrix metalloproteinases (MMPs). However, blockade of the RAS does not improve (and may actually exacerbate) LV remodeling in MR. Interestingly, the investigators and others have shown that ß1-receptor blockade (ß1-RB) is more effective than RAS blockade in attenuating progressive LV remodeling and ECM degradation in MR. Moreover, increased sympathetic drive and inflammation has been identified in patients with chronic MR. ß-RB reduced plasma markers of inflammation in patients with heart failure and resulted in substantial reverse LV remodeling in patients with heart failure. Taken together, activation of the adrenergic nervous system early in the course of volume overload contributes to increased production of reactive inflammatory species (RIS) and that one mechanism underlying the salutary effects of ß-blockade may relate to attenuation of myocardial formation of RIS with subsequent beneficial effects on MMP activation and ECM and LV remodeling and function.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Conditions

Mitral Regurgitation

Intervention

Beta-1 receptor blocker Metoprolol

Location

University of Alabama at Birmingham
Birmingham
Alabama
United States
35294-2180

Status

Active, not recruiting

Source

University of Alabama at Birmingham

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-07-23T21:11:03-0400

Clinical Trials [1169 Associated Clinical Trials listed on BioPortfolio]

A Randomized Clinical Trial of Metoprolol in Participants With Mitral Regurgitation.

Mitral valve regurgitation (leakage of the mitral valve of the heart) is frequent and currently there is no specific medical therapy. Mitral regurgitation is a slowly progressive disease ...

Using Beta Blockers to Treat Mitral Regurgitation

The purpose of this study tests whether a beta-blocker drug will benefit patients with chronic mitral regurgitation.

Observational Study of the Heart Repair Technologies Mitral Bridge in Treating Mitral Valve Regurgitation

Prospective, observational, multi-center trial in which patients with mitral regurgitation sufficient to merit mitral valve repair will receive a surgical transvalvular, intra-annular Mitr...

Tolerability of Metoprolol-Succinate-ER and Carvedilol in COPD

Use of beta-blockers has proven beneficial in patients with hypertension, heart failure, and in people who have suffered a heart attack. The use in patients who have Chronic Obstructive Pu...

Enoximone Plus Extended-Release Metoprolol Succinate in Subjects With Advanced Chronic Heart Failure

Beta-blocker medications have been shown to improve heart function and prolong the lives of patients with chronic heart failure (CHF). Some people with advanced CHF have difficulty taking...

PubMed Articles [7125 Associated PubMed Articles listed on BioPortfolio]

Overview of mitral regurgitation in Europe: results from the European Registry of mitral regurgitation (EuMiClip).

To determine the prevalence of mitral regurgitation (MR) in a large cohort of consecutive patients undergoing clinically indicated echocardiography and to examine the distribution of primary and secon...

Follow-Up of the Novel Free Margin Running Suture Technique for Mitral Valve Repair.

The free margin running suture (FMRS) is a novel technique for nonresection correction of degenerative mitral regurgitation. It was employed in 37 minimally invasive mitral repair cases. We performed ...

The Impact of Mitral Disease Etiology on Operative Mortality Following Mitral Valve Operations.

The patho-etiology of mitral regurgitation (MR) has been suggested as a mediator of outcomes following mitral valve (MV) operations, particularly in ischemic functional mitral regurgitation (IMR). Thi...

A Simplified Technique for Correcting Mitral Valve Regurgitation Via Minimally Invasive Approach.

Mitral valve regurgitation may require complex repair techniques that are challenging in minimally invasive and may expose patients to prolonged cardiopulmonary bypass and cross-clamp times. Here, we ...

Serotonin receptor 2B signaling with interstitial cell activation and leaflet remodeling in degenerative mitral regurgitation.

Mitral valve interstitial cells (MVIC) play an important role in the pathogenesis of degenerative mitral regurgitation (MR) due to mitral valve prolapse (MVP). Numerous clinical studies have observed ...

Medical and Biotech [MESH] Definitions

Backflow of blood from the LEFT VENTRICLE into the LEFT ATRIUM due to imperfect closure of the MITRAL VALVE. This can lead to mitral valve regurgitation.

A cardioselective ADRENERGIC BETA-1 RECEPTOR ANTAGONIST (beta-blocker) that functions as a VASODILATOR through the endothelial L-arginine/ NITRIC OXIDE system. It is used to manage HYPERTENSION and chronic HEART FAILURE in elderly patients.

Hydrogenated alprenolol derivative where the extra hydrogens are often tritiated. This radiolabeled form of ALPRENOLOL, a beta-adrenergic blocker, is used to label the beta-adrenergic receptor for isolation and study.

A subclass of beta-adrenergic receptors (RECEPTORS, ADRENERGIC, BETA). beta-1 Adrenergic receptors are equally sensitive to epinephrine and norepinephrine and bind the agonist dobutamine and the antagonist metoprolol with high affinity. They are found in the heart, juxtaglomerular cells, and in the central and peripheral nervous systems.

Abnormal protrusion or billowing of one or both of the leaflets of MITRAL VALVE into the LEFT ATRIUM during SYSTOLE. This allows the backflow of blood into left atrium leading to MITRAL VALVE INSUFFICIENCY; SYSTOLIC MURMURS; or CARDIAC ARRHYTHMIA.

More From BioPortfolio on "Molecular Mechanisms of Volume Overload-Aim 1(SCCOR in Cardiac Dysfunction and Disease)"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Cardiology
Cardiology is a specialty of internal medicine.  Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...

Radiology
Radiology is the branch of medicine that studies imaging of the body; X-ray (basic, angiography, barium swallows), ultrasound, MRI, CT and PET. These imaging techniques can be used to diagnose, but also to treat a range of conditions, by allowing visuali...


Searches Linking to this Trial